Potent antitumor activity of the acyclic nucleoside phosphonate 9‐(2‐phosphonylmethoxyethyl)adenine in choriocarcinoma‐bearing rats

摘要: The acyclic nucleoside phosphonate 9-(2-phosphonyl-methoxyethyl)adenine (PMEA) is a potent and selective antiretroviral agent which currently evaluated in its oral prodrug form, bis(POM)PMEA (adefovir dipivoxil), phase II III clinical trials human hepatitis B virus (HBV)- immunodeficiency (HIV)-infected individuals, respectively. We have now found that PMEA also inhibitor of growth the highly aggressive choriocarcinoma tumor arising from rat RCHO cells grafted under kidney capsule syngeneic WKA/H rats. In untreated rats, massive invasive tumors, covering whole surface resulting marked enlargement kidney, were observed at day 10 after cell grafting. Daily treatment with 25 mg/kg/ afforded reduction size (i.e., smaller tumors slight, if any, kidney). Increasing dose to 50, 100 or 250 mglkglday resulted gradual increase antitumor effect compound. At highest tested, i.e., mg/kg/day, completely suppressed growth. activity persisted for least days termination drug treatment. addition, delayed 200 started time point where had already developed, stopped further even induced regression tumors. PMPA, closely related structural analogue PMEA, failed inhibit This observation points specificity as an agent. view our findings, therapeutic potential neoplastic diseases appears merit investigation.